There is no doubt that there are genetic, environmental and behavioral components to the expression of oral health status in all populations. Furthermore, it is clear that there will be interactions between these components and that each of these components may be transmissible (in a broad sense) within families. Therefore, in this project we will apply state-of-the-art statistical and molecular genetic approaches to two study samples: a representative W.V. cohort of 500 families, and a subset of approximately 80 "high-risk" families (i.e., ascertained through index through index cases in the top 10% of the distribution of the DMFS index) The ultimate goal of the studies described in this project is to develop an array of functional genetic polymorphisms that are related to oral health, in order to characterize individuals (and populations) as to their genetic risk factors. This array could ultimately be implemented via a DNA chip, or other high throughput platform, for rapid and cost- effective genotyping. To begin to develop such an array, we will focus on approximately 25-30 genes that are known to be important in oral health in the broad categories of growth factors and receptors, homeodomain genes, signaling and transcription factors, xenobiotic detoxification and metabolism, inflammation, and behavior. The Appalachian population has never been characterized with respect to these categories of genes and such characterization will be the first aim of this study. Then, the genotypes at these genetic loci will be analyzed simultaneously with oral health phenotypes, microbiological status, and health behaviors in order to discover the transmission pattern of the phenotypes (adjusted for the effects of the microbiology and behavior covariates) and the potential co- segregation of phenotypes and genotypes, in order to identify the genes that are important in oral health in this population. The major orofacial disease outcome of interest to COHRA is caries, and caries will therefore provide a major focus for the genetic studies outlined in this proposal. However, similar strategies will pertain for the other orofacial phenotypes, such as periodontal status, assessed on the study subjects.